BACKGROUND: Patients with ischemic heart disease may require antianginal and/or antiarrhythmic regimes. These patients may also be candidates for implantable defibrillators. The effects of antiarrhythmics, such as bretylium, or calcium antagonists, such as verapamil, nifedipine, or diltiazem on internal defibrillation efficacy have been inconsistent or are unknown. METHODS AND RESULTS: The effects of bretylium and verapamil on the energy requirements for ventricular defibrillation threshold (DFT) were determined in 92 open-chest anesthetized pigs. Triplicate DFTs were determined before and after intravenous administration of saline or one of four doses of verapamil, or saline or one of three doses of bretylium, in a balanced random order. Bretylium elicited a dose dependent reduction of DFT (F = 2.72 at 3 degrees and 36 degrees of freedom). DFT was significantly reduced with the highest dose of bretylium, (from 5.9 +/- 0.6 J to 4.7 +/- 0.6 J, mean +/- S.E.M.; P < 0.01). However, cardiac massage was sometimes needed at this dose due to low blood pressure immediately after defibrillation. In contrast, there was a positive correlation between DFT and serum verapamil concentration (r = 0.54, P < 0.001). The highest dose of verapamil significantly increased DFT (from 6.3 +/- 0.6 J to 8.2 +/- 1.1 J; P < 0.05), at a serum verapamil concentration of 86.6 +/- 6.8 ng/mL. CONCLUSIONS: These data indicate that bretylium decreases while verapamil increases the minimum energy requirement for internal defibrillation. Caution is warranted in patients who may be hemodynamically comprised and may be candidates for bretylium therapy or in patients who have marginal DFT value who might be candidates for verapamil therapy.